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Molecular Neurobiology

, Volume 53, Issue 1, pp 120–131 | Cite as

Intrathymic Tfh/B Cells Interaction Leads to Ectopic GCs Formation and Anti-AChR Antibody Production: Central Role in Triggering MG Occurrence

  • Xiaoyan Zhang
  • Shasha Liu
  • Ting Chang
  • Jiang Xu
  • Chunmei Zhang
  • Feng Tian
  • Yuanjie Sun
  • Chaojun Song
  • Wei Yi
  • Hong Lin
  • Zhuyi LiEmail author
  • Kun YangEmail author
Article

Abstract

Myasthenia gravis is a typical acetylcholine receptor (AChR) antibody-mediated autoimmune disease in which thymus frequently presents follicular hyperplasia or thymoma. It is now widely accepted that the thymus is probably the site of AChR autosensitization and autoantibody production. However, the exact mechanism that triggers intrathymic AChR antibody production is still unknown. T follicular helper cells, recently identified responsible for B cell maturation and antibody production in the secondary lymphoid organs, were involved in many autoimmune diseases. Newly studies found T follicular helper (Tfh) cells increased in the peripheral blood of myasthenia gravis (MG). Whether it appears in the thymus of MG and its role in the intrathymic B cells help and autoantibody production is unclear. Therefore, this study aims to determine in more detail whether Tfh/B cell interaction exist in MG thymus and to address its role in the ectopic germinal centers (GCs) formation and AChR antibody production. We observed the frequency of Tfh cells and its associated transcription factor Bcl-6, key cytokine IL-21 enhanced both in the thymocytes and peripheral blood mononuclear cells (PBMCs) of MG patients. In parallel, we also showed increased B cells and autoantibody titers in MG peripheral blood and thymus. Confocal microscope results demonstrated Tfh and B cells co-localized within the ectopic GCs in MG thymus, suggesting putative existence of Tfh/B cells interaction. In vitro studies further showed dynamic behavior of Tfh/B cells interaction and Tfh cells induced autoantibody secretion might through its effector cytokine IL-21. Altogether, our data demonstrated that intrathymic Tfh/B cells interaction played a key role in thymic ectopic GCs formation and anti-AChR antibody production, which might trigger MG occurrence.

Keywords

Myasthenia gravis Follicular helper T cells Thymus Anti-acetylcholine receptor antibody Germinal centers 

Notes

Acknowledgments

This work has been supported by the National Natural Science Foundation of China (grants 31270952, 81171977, 81102217, and 31100620). We thank the Department of Thoracic surgery, Tangdu Hospital, and the Department of Cardiovascular Surgery, Xijing Hospital, for the provision of thymus specimen.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Xiaoyan Zhang
    • 1
    • 2
    • 3
  • Shasha Liu
    • 1
    • 2
  • Ting Chang
    • 1
  • Jiang Xu
    • 1
  • Chunmei Zhang
    • 2
  • Feng Tian
    • 4
  • Yuanjie Sun
    • 2
  • Chaojun Song
    • 2
  • Wei Yi
    • 5
  • Hong Lin
    • 1
  • Zhuyi Li
    • 1
    Email author
  • Kun Yang
    • 2
    Email author
  1. 1.Department of NeurologyTangdu Hospital, The Fourth Military Medical UniversityXi’anChina
  2. 2.Department of ImmunologyThe Fourth Military Medical UniversityXi’anChina
  3. 3.Department of NeurologyLanzhou General Hospital, Lanzhou Command of CPLALanzhouChina
  4. 4.Department of Thoracic SurgeryTangdu Hospital, The Fourth Military Medical UniversityXi’anChina
  5. 5.Department of Cardiovascular SurgeryXijing Hospital, The Fourth Military Medical UniversityXi’anChina

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